The invention relates to an apparatus for determining a parameter indicative of the progress of an extracorporeal blood treatment (referred to as effectiveness parameter), in particular a purification treatment whose purpose is to alleviate renal insufficiency, such as—without limitation—hemodialysis or hemodiafiltration. It is also disclosed a method of determining said parameter indicative of the progress of an extracorporeal blood treatment. For instance, the parameter may be one of:                the concentration in the blood of a given solute (for example, sodium),        the actual dialysance D or the actual clearance K of the exchanger for a given solute (the dialysance D and the clearance K representing the purification efficiency of the hemodialyzer or hemofilter used in the blood treatment),        the dialysis dose administered after a treatment time t, which, according to the work of Sargent and Gotch, may be linked to the dimensionless ratio Kt/V, where K is the actual clearance in the case of urea, t the elapsed treatment time and V the volume of distribution of urea, i.e. the total volume of water in the patient (Gotch F. A. and Sargent S. A., “A mechanistic analysis of the National Cooperative Dialysis Study (NCDS)”, Kidney Int. 1985, Vol. 28, pp. 526-34). The dialysis dose—as above defined—is an integrated value ∫K(t)dt/V across a time interval, e.g. the dose after treatment time tn is the integral from the beginning of treatment until time instant tn.        
In an haemodialysis treatment a patient's blood and a treatment liquid approximately isotonic with blood flow are circulated in a respective compartment of haemodialyser, so that, impurities and undesired substances present in the blood (urea, creatinine, etc.) may migrate by diffusive transfer from the blood into the treatment liquid. The ion concentration of the treatment liquid is chosen so as to correct the ion concentration of the patient's blood.
In a treatment by haemodiafiltration, a convective transfer by ultrafiltration, resulting from a positive pressure difference created between the blood side and the treatment-liquid side of the membrane of an hemodiafilter, is added to the diffusive transfer obtained by dialysis.
It is of interest to be able to determine, throughout a treatment session, one or more parameters indicative of the progress of the treatment so as to be able, where appropriate, to modify the treatment conditions that were initially fixed or to at least inform the patient and the medical personnel about the effectiveness of the treatment.
The knowledge of one or more of the following parameters may make it possible to follow the progress of the treatment, and for instance may allow assessing the suitability of the initially fixed treatment conditions:                the concentration in the blood of a given solute (for example, sodium),        the actual dialysance D or the actual clearance K of the exchanger for solute (the dialysance D and the clearance K representing the purification efficiency of the exchanger),        the dialysis dose administered after a treatment time Kt/V, where K is the actual clearance in the case of urea, t the elapsed treatment time and V the volume of distribution of urea.        
The determination of these parameters requires precise knowledge of a physical or chemical characteristic of the blood. As it can be understood, determination of this characteristic cannot in practice be obtained by direct measurement on a specimen for therapeutic, prophylactic and financial reasons. Indeed, it is out of the question taking—in the course of a treatment—multiple specimens necessary to monitor the effectiveness of the treatment from a patient who is often anemic; furthermore, given the risks associated with handling specimens of blood which may possibly be contaminated, the general tendency is to avoid such handling operations; finally, laboratory analysis of a specimen of blood is both expensive and relatively lengthy, this being incompatible with the desired objective of knowing the effectiveness of a treatment while the treatment is still ongoing.
Several methods have been proposed for in vivo determining haemodialysis parameters without having to take measurements on blood samples.
Document EP 0547025 describes a method for determining the concentration of a substance, such as sodium, in a patient's blood subjected to a haemodialysis treatment. This method also makes it possible to determine the dialysance D—for example for sodium—of the haemodialyser used. The method comprises the steps of circulating a first and a second haemodialysis liquids having different sodium concentrations in succession through the haemodialyser, measuring the conductivity of the first and second dialysis liquids upstream and downstream of the haemodialyser, and computing the concentration of sodium in the patient's blood (or the dialysance D of the haemodialyser for sodium) from the values of the conductivity of the liquid which are measured in the first and second dialysis liquids upstream and downstream of the haemodialyser.
Document EP 0658352 describes another method for the in vivo determination of haemodialysis parameters, which comprises the steps of: making at least a first and a second treatment liquids, having a characteristic (the conductivity, for example) associated with at least one of the parameters (the ion concentration of the blood, the dialysance D, the clearance K, Kt/V, for example) indicative of the treatment, flow in succession through the haemodialyser, the value of the characteristic in the first liquid upstream of the exchanger being different from the value of the characteristic in the second liquid upstream of the hemodialyzer; measuring, in each of the first and second treatment liquids, two values of the characteristic, respectively upstream and downstream of the hemodialyzer; making a third treatment liquid flow through the hemodialyzer while the characteristic of the second liquid has not reached a stable value downstream of the hemodialyzer, the value of the characteristic in the third liquid upstream of the hemodialyzer being different from the value of the characteristic in the second liquid upstream of the hemodialyzer; measuring two values of the characteristic in the third liquid, respectively upstream and downstream of the hemodialyzer; and computing at least one value of at least one parameter indicative of the progress of the treatment from the measured values of the characteristic in the first, second and third treatment liquids.
Another method for the in vivo determination of the haemodialysis parameters which does not require taking measurements on blood samples is described in document EP 0920877. This method includes the steps of: making a treatment liquid flow through the exchanger, this treatment liquid having a characteristic which has an approximately constant nominal value upstream of the exchanger; varying the value of the characteristic upstream of the exchanger and then re-establishing the characteristic to its nominal value upstream of the exchanger; measuring and storing in memory a plurality of values adopted by the characteristic of the treatment liquid downstream of the exchanger in response to the variation in the value of this characteristic caused upstream of the exchanger; determining the area of a downstream perturbation region bounded by a baseline and a curve representative of the variation with respect to time of the characteristic; and computing the parameter indicative of the effectiveness of a treatment from the area of the downstream perturbation region and from the area of an upstream perturbation region bounded by a baseline and a curve representative of the variation with respect to time of the characteristic upstream of the exchanger.
With the aim of further improving the above methods, document US 2001004523 describes a solution for continuously determining a parameter (D, Cbin, K, Kt/V) indicative of the effectiveness of an extracorporeal blood treatment comprising the steps of: causing a succession of sinusoidal variations in the characteristic (Cd) a treatment liquid upstream of the exchanger, continuously storing in memory a plurality of values (Cdin1 . . . Cdinj . . . Cdinp) of the characteristic (Cd) upstream of the exchanger, measuring and continuously storing in memory a plurality of values (Cdout1 . . . Cdoutj . . . Cdoutp) adopted by the characteristic (Cd) downstream of the exchanger in response to the variations in the characteristic (Cd) which are caused upstream of the exchanger, computing—each time that a predetermined number of new values (Cdoutj) of the characteristic (Cd) downstream of the exchanger has been stored—a parameter (D, Cbin, K, Kt/V) indicative of the effectiveness of the extracorporeal blood treatment, from a first series of values (Cdin) of the characteristic (Cd) upstream of the exchanger, from a second series of values (Cdoutj) of the characteristic (Cd) downstream of the exchanger.
Although the above methods have been implemented, they may have certain limitations.
The above described methods require a modification of the value of a characteristic of the dialysis liquid (the conductivity, for example) and then the re-establishment of this characteristic to its initial value, which is generally the prescribed value for the treatment. Since, deviations from the prescription are not desirable and since the above described methods require a duration of the introduced modification, it derives that the effectiveness parameter measure may be carried out only few times during a treatment.
Furthermore, the above methods require the control system of the blood treatment apparatus to prevent execution of tasks, other than the one for measuring the effectiveness parameter, which may affect the concerned characteristic (conductivity/concentration) of the dialysis fluid at least until the complete measurement of the values taken by the conductivity/concentration downstream the dialyzer has been made. For instance, the user will not be allowed to execute a change prescription task while the control system is executing the effectiveness parameter detection. Moreover, while the control system is executing the effectiveness parameter detection, the control system will not execute other tasks taking an active control on the conductivity/composition of the dialysis liquid (e.g. tasks acting on the sodium concentration of the dialysis liquid in response to detection of certain parameters such as blood concentration). In other words, during the entire process of changing the conductivity/concentration of the dialysis liquid upstream the dialyzer or hemofilter and measuring the corresponding downstream conductivity/concentration change, the control system of the dialysis machine does not allow execution of other tasks which could affect the dialysis liquid conductivity or composition, thereby limiting flexibility of operation of the dialysis machine.
Moreover, the methods described above are sensitive to artifacts that may be present in the conductivity measured downstream the dialyzer which may be caused by a number of factors (e.g. bubbles present in the dialysis circuit, activation/deactivation of certain actuators such as pumps, opening or closing of valves, etcetera).
Furthermore, the characteristic in the liquid downstream the dialyzer may be difficult to accurately be measured, due to a number of factors. Indeed, in case of a step shaped upstream perturbation it may be difficult to measure the asymptotic value of the response unless measurements for the downstream conductivity are taken for a relatively long time. On the other hand, in case of a sinusoidal upstream perturbation which never leads to any equilibrium state it may be difficult to properly interpret sensor detections.
Moreover, the hydraulic delay, the damping effect caused by the dialyzer or hemofilter, the effect of the blood conductivity/concentration on the value of the baseline conductivity downstream the dialyzer of hemofilter, and the noise introduced by the machine and its components may render further difficult interpretation of the signals detected by the sensors, particularly in presence of a continuously varying perturbation.
It is therefore an object of the present invention to provide an apparatus and a method configured reliably calculate an effectiveness parameter a plurality of times during treatment without substantially impairing on prescription delivered to the patient and minimally affecting the operation flexibility of the blood treatment apparatus.
Moreover, it is an auxiliary object providing a method and an apparatus which are not very sensitive to incidents or noise or accidental detection errors which may arise during the measurement.
Additionally, it is an object providing a method and an apparatus which may be implemented with no need of high computational power.
Another auxiliary object is an apparatus capable of operating in a safe manner.
A further auxiliary object is an apparatus capable of automatically calculate the effectiveness parameter and inform the operator accordingly.